Murphy, activated from the disabled list before the game, drove in the winning run with a bases-loaded, pinch-hit single in the 10th inning, and the Indians defeated the Chicago White Sox 2-1 on Friday night.
Murphy, who pulled a right oblique muscle Aug. 9, lined a 1-2 pitch to center off Ronald Belisario that landed in front of center fielder Adam Eaton to score pinch runner Chris Dickerson and give the Indians their 11th walk-off win of the season.
Murphy had no opportunity to ease his way back into action after missing nearly a month. His first at-bat came with the game on the line and his team battling to stay in the playoff race.
"You never figure that you'd be in that situation, but those are the most fun in baseball," he said.
The Indians, coming off a series in which they lost three of four against Detroit, are six games behind Kansas City in the AL Central. Cleveland is also a factor in the crowded wild-card race.
"Every game is the most important game of the year," Murphy said. "It would be nice to be in a little better spot, but we're still in striking distance. We need to go out and win every single day."
Murphy was mobbed his teammates but made sure to protect his rib area.
"After I hit first, I thought, 'Oh no,' but I think they knew to take it easy on me," he said.
Shortstop Leury Garcia finally retrieved the ball and threw it in as Gomes slid into third.
"The desire to want to be at third is what was big," Indians manager Terry Francona said. "He's not the fastest guy in the world, but right out of the box, he was going for it."
Michael Bourn was intentionally walked before Eric Surkamp issued an intentional walk to Lonnie Chisenhall that loaded the bases. Surkamp battled back from a 3-1 count to strike out Jason Kipnis before Murphy, batting for Roberto Perez, delivered.
Chen-Chang Lee (1-1) worked out of a bases-loaded, one-out jam in the 10th.
Chicago ace Chris Sale allowed one run in six innings, lowering his league-best ERA to 2.09.
Indians rookie T.J. House matched Sale, giving up one run and striking out seven in seven innings.
Ramirez left the game after being hit on the left foot by a pitch from House in the fifth. White Sox manager Robin Ventura said Ramirez has a bone bruise and it's possible he could play Saturday.
Ventura expects first baseman Paul Konerko (broken bone in his left hand) to play again this season. The 18-year veteran could resume baseball activities in a week.
Bourn and Kipnis -- both left-handed hitters -- weren't in the lineup. Bourn is hitless with three strikeouts in five at-bats against Sale while Kipnis is 4-for-14 versus the ace lefty.
The Indians acquired OF J.B. Shuck from the Los Angeles Angels on Friday for cash considerations. Shuck, a left-handed hitter, batted .167 in 22 games this season before the Angels designated him for assignment Tuesday. He hit .293 in 129 games last season.
Indians: Murphy came off the 15-day DL on Friday afternoon. He had one hit in six at-bats in two games at Triple-A Columbus on a rehab assignment.
Indians: RHP Corey Kluber (13-9) has lost his past three starts. He ranks third in the American League with 215 strikeouts and 195 1/3 innings.