Mathile was born the oldest child of Wilbert "Bill" Ray Mathile and Helen Good Mathile (married in 1939) in the North West Ohio town of Portage, where his parents owned a 40-acre farm.

On July 7, 1962, he married MaryAnn Maas, the girl he had dated since noticing the Cheerleader rooting for a rival high school years earlier in Custar, Ohio. They have five children, and live in Brookville, Ohio.

In 1970, dissatisfied with his stable corporate position despite the responsibility of supporting a young family, Mathile made the decision to accept a leadership role at a small, regional pet food manufacturer: The Iams Food Company in Dayton, Ohio. To raise awareness of Iams' product, which contained much more protein than competitors' cereal-based dog foods, Mathile spent weekends at dog shows, handing out samples that his children helped him package in their basement. In 1975, after shortages of ingredients almost drove the company under, Mathile purchased half ownership of the company from founder and owner Paul Iams for $100,000. Mathile convinced Paul Iams that the company needed to build its own Manufacturing plant.

During his early tenure, Mathile oversaw The Iams Company's rapid growth. With his wife Mary's encouragement, Mathile purchased the remaining ownership shares from Iams in 1982, becoming sole owner and CEO. At the time, the company had $13 million in sales.

Mathile was known within the company for knowing the names of employees and their spouses, children, and pets, even as the company became an international firm with a staff of nearly 2,000. He often solicited employees' advice and listened to their concerns, but he also enlisted the help of outside experts, such as Tom MacLeod (a former PepsiCo executive), who became President and chief operating officer in 1990. These approaches enabled The Iams Company to achieve a strong position in the premium pet food market and sustain rapid growth both domestically and internationally.

Eventually, Mathile named MacLeod CEO and became chairman of the board. By 1999, Mathile had grown The Iams Company to a 5.7% share of the U.S. pet food market and international sales of 100 different products in 75 countries. After a lengthy search, he sold the privately held, family-owned company to international conglomerate Procter & Gamble for $2.3 billion. Mathile based his decision in large part on the belief that P&G shared his commitment to product quality, Iams employees and customers, and the Dayton community. He distributed $100 million of the sale proceeds among Iams employees, committed $100 million to fund large-scale, community projects in the Dayton area, and distributed substantial, equal portions to his adult children.

From the outset, Mathile focused strongly on product quality, research and development, and customer outreach, including marketing efforts targeting pet owners, high-end breeders, and veterinarians. He offered a 100 percent money-back guarantee to any customer who wasn't satisfied and established a customer support department equipped to answer consumer questions about their pets — even on topics unrelated to pet food, such as handling grief over the loss of a pet. He also established a strong national distributor network. Insisting that vendors be paid within 30 days ensured that The Iams Company had the best supplies available — even during shortages. Mathile also honored Paul Iams' commitment to science by funding a new research and development center, which worked to ensure that dogs and cats received the best nutrition possible from Iams and Eukanuba.