"Off the bat I thought I got it, then it took a hard left and I wasn't sure," Ellis said. "This one I had my doubts about. We really needed that."
Ellis hit the first pitch from Chris Bootcheck (0-1) off the left-field foul pole for his second career game-ending homer and his third grand slam. Ellis connected to nearly the same spot May 7 with a game-ending homer in a 6-5, 10-inning win over Baltimore - even nicking the foul pole on that one.
"It's tough to swallow," Bootcheck said.
It was the fifth walk-off grand slam by the A's and first since Mark McGwire did it on June 30, 1995, also against the Angels. Ellis' sixth homer of the year ended a 3-hour, 53-minute game and made sure Oakland avoided a three-game sweep against its AL West rival.
The A's can now head into their off day Monday on a high note, then get ready to host the New York Yankees on Tuesday.
After consecutive one-out singles by Gregorio Petit and Rajai Davis - neither of whom started - Bootcheck struck out Emil Brown for the second out before walking Travis Buck to load the bases and bring up Ellis.
Bootcheck hadn't pitched since May 30.
"It's a tough role. It's probably an overlooked role," Angels manager Mike Scioscia said. "He works hard to stay sharp."
Davis also stole a base and scored on Eric Chavez's RBI double in the seventh off Darren Oliver that made it 3-all.
"That was awesome," Davis said. "I was believing we were going to pull it out that inning. We fought, we fought and we fought. You've got a chance when you don't give up. They had opportunities to put us away."
The Angels had chances in the ninth against Huston Street, but Vladimir Guerrero's fly ball to right didn't go far enough to score Howie Kendrick from third. Torii Hunter struck out, leaving runners on second and third.
Brad Ziegler (1-0) pitched 1 2-3 hitless innings for his first major league win. He got the lineup card as a keepsake.
"This is the kind of game you're never going to forget. I've never seen a walk-off granny before," he said.
Each of the first two games of the series were decided by two runs, and the Angels' other five wins during their streak were by one run.
"It would have been tough to lose all three games," said Ellis, who singled in the second and then went hitless in his next four at-bats before the homer. "The best part of baseball is you always have another at-bat."
Guerrero hit a go-ahead, two-run homer in the fourth and Gary Matthews Jr. added an RBI single in the inning against Rich Harden.
The Angels had their division lead over Oakland cut to 4½ games. Los Angeles still concluded an impressive 5-1 road trip.
"You have to stay positive," Hunter said. "A five-out-of-six road trip isn't bad."
Angels starter Ervin Santana struck out the side in order in the sixth and appeared poised for his ninth victory in 13 starts this year. He matched his season high with nine strikeouts while walking three in 6 1-3 innings.
Chavez's RBI single in the first snapped Santana's streak of 23 consecutive innings without allowing an earned run against the A's. The right-hander yielded seven hits and two runs.
When Carlos Gonzalez hit an RBI single in the fourth to pull Oakland to 3-2, the rookie ended his stretch of seven straight extra-base hits - all doubles - to start his career. Called up on May 30, he became the first major leaguer since Johnny Mize in 1936 to begin his big league career with each of his first seven hits going for extra bases.
Harden matched his season high with nine strikeouts. He allowed three runs and six hits in six innings with three walks in his sixth start since coming off the disabled list May 11 after a shoulder injury.
The hard-throwing right-hander struck out the side in the first on nine pitches, the first pitcher in the majors to do so since Atlanta's Buddy Carlyle on July 6, 2007. The last AL pitcher to do it was Pedro Martinez on May 18, 2002, with Boston. Harden is the first A's pitcher to do it since Lefty Grove on Sept. 27, 1928. Guerrero hit his eighth home run this season, 19th of his career against the A's and second off Harden. Garret Anderson ended an 0-for-16 stretch with a two-out single in the fifth. Bobby Crosby, Oakland's shortstop, left after the eighth with a slightly sprained right ankle. He hopes to play Tuesday against New York. Notes: Angels 3B Chone Figgins (hamstring) is scheduled to begin a rehab assignment for Triple-A Salt Lake on Monday. ... Oakland RHP Santiago Casilla, on the DL recovering from an elbow injury, threw 29 pitches in a simulated game.