Mexican artist Francisco Toledo in 2015, at an exhibition in the Mexico City subway system. (Alfredo Estrella/AFP/Getty Images)

Francisco Toledo, one of Mexico’s most renowned artists, whose work fused nature and myth while drawing international attention to the indigenous traditions of southern Mexico, died Sept. 5 at his home in Oaxaca City. He was 79.

His death was announced by Mexican President Andrés Manuel López Obrador, who called him “a true defender of nature, customs and traditions of our people.”

His daughter, Sara López Ellitsgaard, said the cause was cancer.

Mr. Toledo was known as both a master artist and an ambassador for the southern state of Oaxaca, an impoverished hub of indigenous language and culture that he helped elevate into a dynamic center of the Mexican art scene.

The son of a Zapotec tanner and shoemaker, he worked as a painter, photographer, lithographer, engraver, sculptor, ceramist and tapestry designer, all while developing a reputation as a fiery defender of Oaxacan tradition. He sometimes described himself as a grillo (Zapotec for cricket), using a nickname for Oaxacans who — in addition to dining on grasshopper, a local delicacy — are “troublemakers and can’t sit still.”

When McDonald’s planned to open a new location in Oaxaca City’s historic square, he announced he would protest naked in front of the proposed site. His clothes stayed on, but he gave away free tamales alongside hundreds of demonstrators, chanting, “Tamales, yes! Hamburgers, no!”

Mr. Toledo in 2014, flying kites he designed with the portraits of 43 missing students who were abducted by police and disappeared in 2014. (Jorge Luis Plata/Reuters)

Other political efforts dovetailed with his art, which veered from grand 80-foot-long sculptures to whimsical hand puppets and felt hats. After 43 students in the rural state of Guerrero were abducted by police and disappeared in 2014, Mr. Toledo painted their portraits on kites, flying them with a group of children as a memorial to the victims.

For the most part, however, he avoided the overt political messaging that dominated Mexican art in his youth, when muralists José Clemente Orozco, Diego Rivera and David Alfaro Siqueiros painted large-scale works on national themes.

A member of what is sometimes called the “breakaway generation” of Mexican art, Mr. Toledo rose to prominence in the 1960s with small watercolors that were often humorous or erotic, featuring a menagerie of animals — crabs, cows, coyotes, jaguars, alligators, turtles, toads, monkeys, grasshoppers and scorpions. Mysterious human-animal figures abounded, and his creatures often seemed drawn from myths and fables.

“What I like most about Mr. Toledo’s art is its charming awkwardness; his images capture the playful immediacy of children’s drawings, with their alluring, unexpected combination of fantasy and sincerity,” wrote former New York Times journalist Benjamin Genocchio, reviewing a 2007 exhibition at Princeton University. “They cast an immediate, joyous spell over viewers, their disarmingly simple appearance gradually giving way to a deeper understanding of an intimate, abstract exploration of the natural world.”

Mr. Toledo drew on the pre-Hispanic artistic traditions of the Isthmus of Tehuantepec, which divides the Pacific from the Gulf of Mexico, and studied the work of old masters (Rembrandt and Francisco Goya) as well as experimental modernists (Marc Chagall and James Ensor).

Mr. Toledo in 2008, working on his sculpture “La Lagartera,” an 80-foot-long reptile made of steel and plaster. (Tomas Bravo/Reuters)

He painted on tortoise shells and ostrich eggs, created scores of self-portraits and made a frequent subject of Benito Juárez, a fellow Oaxacan Zapotec who served as president of Mexico in the mid-19th century. One image showed the national hero ice-skating (poorly) in New Orleans, which a youthful Mr. Toledo had apparently believed was much farther north; another showed Juárez being turned into a grasshopper by women in the town of Juchitán, where Juárez had violently suppressed a rebellion while serving as state governor.

Among Mr. Toledo’s last exhibits was “Duelo” (Mourning), which featured 95 ceramic pieces, many tinted a hellish red, showing disembodied limbs or inhuman figures, mouths agape in horror. “With everything that one hears in the news, in the newspapers, little by little this pushed me to do an exhibit on the theme of violence,” he told the Los Angeles Times. “And red [colors] that I had never used began to appear, colors of blood. None of this was planned.”

Francisco Benjamín López Toledo was born July 17, 1940. In interviews, he alternately said he was born in Mexico City and Juchitán. Some news reports say he was born in Minatitlán, in the southeastern state of Veracruz, where by all accounts the family eventually settled — and where a young Francisco romped through forests and turtle-filled marshes while his father made alligator-skin belts at his shop.

“My father’s love for furs and animal skins later had an impact on my own work,” he told Bomb magazine in 2000. “At home there would always be all types of animal skins that he had bought or that people gave him. I’ve always had a love for furs and skins and many of the animal drawings I’ve made come from these memories.”

Mr. Toledo went to art school in Mexico City, and by 19 had his first exhibition. It traveled to Fort Worth, and soon he made his own way to Paris, where he learned copper engraving from English artist Stanley William Hayter, befriended Mexican writer Octavio Paz and studied under Zapotec painter Rufino Tamayo.

“It was wonderful. Tamayo invited me to his house and he started to sell my paintings,” Mr. Toledo later told the Guardian. “When the collectors would come to visit him, he’d say, ‘Here is a young painter whose paintings are much cheaper than you can buy mine for.’ ”

In 1965, he returned to Oaxaca, where he became known as “El Maestro.” For years he maintained the look of a rumpled wild man or wizened elder, with a bushy beard and a simple outfit of cotton shirt, white pants and leather sandals. He rarely spoke with the media but acquired a local celebrity, partly through philanthropic work driven by six-figure sales of his art.

Mr. Toledo established the Graphic Arts Institute of Oaxaca, now led by his daughter Sara, and also helped form a contemporary art museum, photography center, library for the blind and environmental organization.

His marriages to Olga de Pav Vicente and Elisa Ramírez ended in divorce. Survivors include his wife of 32 years, Trine Ellitsgaard, a Danish-born weaver; a daughter from his first marriage, poet Natalia Toledo; two children from his second marriage, Laureana Toledo, an artist, and Jerónimo López Ramírez, a tattoo artist; two children from his third marriage, Sara López Ellitsgaard and Benjamín López Ellitsgaard; four sisters; and two grandchildren.

Although Mr. Toledo’s work often suggested a union between humans and nature, he spoke of humanity’s “drive toward total destruction” and could be pessimistic about the prospects of preserving natural spaces like the marshes he delighted in as a boy.

“I do what I do without any hope of a lasting or significant effect,” he told Bomb. “I do these things because I feel it’s my duty and because I have the means to do them at this moment in time. … What will happen will happen no matter what I do. What we do by day to conserve gets erased at night by TV or movies or radio. So to talk of hope is somewhat in vain.”