And for the last six seasons with Boston -- some of the best years in the history of the Red Sox -- Mills was Francona's lieutenant, serving as bench coach. So on Tuesday, when Mills was named manager of the Astros, the professional pairing of two close friends came to an end.
"I'm proud for him," Francona said by telephone on Tuesday. "He's one of my best friends, not just in the game but in life. We've been together for 30 years. It's a little bit bittersweet, because it's our loss, [but] their gain far outweighs how I feel about losing him."
In his quest to land the Astros' job, Mills had no bigger supporter than Francona.
"I've never seen an endorsement like Terry gave Brad," said Astros owner Drayton McLane at the news conference to unveil Mills.
An ecstatic Mills thanked the Red Sox shortly after being invited to the podium by McLane.
"I just left an organization, the Boston Red Sox, that I owe a lot to, starting with [principal owner] John Henry, [chairman] Tom Werner, [president/CEO] Larry Lucchino and everybody in that organization," said Mills. "They were very special to me the six years I was over there.
"[General manager] Theo Epstein and his staff, they were absolutely outstanding. And it goes without saying, Terry Francona. The experience that all of them and Terry were able to give me helped set me up for this today. I am deeply proud to say that I was involved with them at that time, and I appreciate it, and I want to thank them very much."
In recent years, Francona had openly lamented that Mills didn't seem to pop up on the radar screens of teams that had managerial vacancies. But things started to change last winter, when Mills was granted an interview by the Seattle Mariners.
And with their opening, the Astros identified him as a candidate right out of the gate.
Francona and Mills both worked under current Astros GM Ed Wade when they were in Philadelphia. Though Wade dismissed Francona as Phillies manager following the 2000 season, the two men have a good relationship and were in contact throughout this process.
"[We were in touch] a little bit," Francona said. "Eddie, he did a good job. He asked a lot of good questions, but personally, I think it's a good fit. I know both of them. I have a lot of respect for both of them, and I think it's a great fit."
Things will be different for Francona when he arrives at Fort Myers, Fla., for Spring Training and doesn't have Mills by his side. For Mills was the de facto organizer of camp, charting out which field everyone would be on for virtually every moment weeks ahead of time.
"I've probably taken it for granted that everybody is where they're supposed to be because he's so good at it," Francona said. "We'll certainly have to make some adjustments. But his gain far outweighs any adjustments we have to make. Millsy embodies so much of what is good in baseball. For him to get an opportunity, it sure is nice. It sure is exciting for all of us."
Francona thinks that the timing is perfect for the 52-year-old Mills to get his chance to manage a Major League team.
"I think he's ready," he said. "He's been ready. That's subjective, but he's been working his whole life toward this. When he was second in charge, he did a great job. Now he's going to be making the decisions, and he'll do a great job. You can't find a better guy. He deserves this opportunity. Again, I hope he takes it and runs with it. I'm thrilled for him."
As for who will take the spot next to Francona on the Boston bench, that remains to be seen.
"Oh, I don't know," Francona said. "Millsy got this job, I think, an hour ago. We'll let things settle down here and see what's going on. We think we've got a healthy organization, and we've got good coaches in place. Theo and I, we'll sit down and see what makes sense for us going forward, but I don't think there's any rush."
Much like Francona on Tuesday, it was Epstein who lost a confidant to a better opportunity on Monday, as Jed Hoyer was named GM of the Padres.
"Jed has been an immensely valuable member of our Baseball Ops team since joining the Red Sox in 2002," Epstein said on Monday. "His combination of analytical ability, feel for the game, interpersonal skills and creativity helped make us tick, and he played a role in virtually every major decision we have made. His loyalty and friendship will be missed, and we know he will continue to make us proud."
Francona made it clear that in such cases as Mills and Hoyer, the sweet far outweighs the bitter for the organization that lost them.
"The pride outweighs everything," Francona said, "and the happiness for your friends. I think you know, when you hire good people, they're going to leave. But my goodness, it's such a good feeling to see this happen. We have some work to do because of it, but I hope that happens more often, because it's such a good feeling."
Ian Browne is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.