He was 1–2 with a 3.29 earned run average and one save as a relief pitcher when he made his first start on September 25 against the Los Angeles Dodgers.

He was 4–3 with a 3.55 ERA and six saves in 1967 when an injury to Bob Gibson (a broken leg suffered at the hands of a Roberto Clemente line drive) forced him into the starting rotation.

In Yastrzemski's first at-bat in game three, Briles hit him on the calf with a pitch causing an argument at home plate between the two teams' managers.

[9] Briles went 15–13 with a 3.52 ERA in 1969 as the Cards slumped to fourth place in the newly formed National League East.

[11] Just as pitchers and catchers were reporting the following season, he and Vic Davalillo were sent to the Pittsburgh Pirates for Matty Alou and George Brunet.

Though he pitched very well, (3-1 with two shutouts, a complete game and a 1.74 ERA) he did not make an appearance in the 1971 National League Championship Series against the San Francisco Giants.

Briles, who studied drama at Santa Clara, became just as famous off the field in Pittsburgh with a nightclub act in which he sang and told jokes.

On his way to training camp in Bradenton, Florida in 1972, Briles made a pit stop at a hockey game between the St. Louis Blues and Boston Bruins.

[17] He was traded with Fernando González to the Kansas City Royals for Kurt Bevacqua, Ed Kirkpatrick and minor league first baseman Winston Cole at the Winter Meetings in Houston on December 4, 1973.

[18] Shortly after the trade, Briles released the single "Hey Hank" b/w "Soft the Summer Wind Blows" on Capitol Records.

After missing the entire month of June, he returned on the Fourth of July, but was forced to leave his first game back with soreness in his elbow.

With a staff that also included Hall of Famers Gaylord Perry and Bert Blyleven, Rangers pitching kept them in first or near first place in the American League West through May.

With Doyle Alexander and Dock Ellis added to the starting rotation in 1977, Briles was relegated to the bullpen and fifth starter duties.

[28] Though he failed to make the club, he appears in a Saturday Night Live skit featuring actual Mets players.

Fictional Dominican second baseman Chico Escuela (portrayed by Garrett Morris) was also with the Mets that Spring attempting to make a comeback at 41 years old.

[29] Following his retirement as a player, Briles worked as a television color commentator for the Pirates,[30] Seattle Mariners, and USA Network.

Briles collapsed and died of an apparent heart attack in Orlando, Florida, while participating in the annual Pirates alumni golf tournament.