There are some nights when Gov’t Mule walks onstage, checks out the crowd and, depending on the vibe they get, say to hell with the setlist.

“Sometimes it’s based on what we played last night or the night before,” singer-guitarist Warren Haynes says. “Sometimes it’s about what we feel like playing or what kind of audience we’re perceiving that it’s going to be that night. But if we feel like the plan is not connecting, then we’ll just call an audible and completely ignore the setlist. I think the freedom that that gives us is something we all love.”

It takes guts to work without a net in front of thousands of people, but it’s business as usual for Gov’t Mule, a band that can blend muscular Southern rock with gritty, down-in-the-gutter blues, delicate country-folk, and jazz-fueled improvisation. It probably also helps that they’ve been at it for almost 25 years, a number that no one’s more surprised about than Haynes.

“When (the late bassist and band co-founder) Allen Woody and I started Gov’t Mule, it was a side-project,” Haynes says. “Allen and I were full-time members of the Allman Brothers Band. But we had a fair amount of time on our hands to do other things, so we just started doing Mule for fun. We didn’t really have any aspirations of it continuing — we were just kind of seeing where it went, and it grew wings and became more than we expected. We didn’t expect it to last five years, much less 25.”

The band’s self-titled 1994 debut album ended up getting such a strong response that, by the late 1990s, both Haynes and Woody had left the Allmans to attempt to go full-time with Mule, but then tragedy struck in 2000, once again leaving the band’s future unclear.

“In 1997 we realized that in order for the band to be what we were starting to see that it could be, we needed to start focusing on it,” Haynes says. “And at that time, the original members of the Allman Brothers were not getting along very well. We were all having a good time writing and rehearsing and recording, all the things that weren’t going on in the Allman Bros camp. But then Allen Woody passed away, and that was such a big deal that my immediate reaction was that that was the end of the band.”

In fact, Gov’t Mule was in such an uncertain state in the wake of Woody’s death that Haynes rejoined the Allman Brothers Band after a call from Gregg Allman. But his friends and peers in the music industry, not to mention a staggering list of temporary bassists, refused to let Haynes and drummer Matt Abts put their band to rest.

“We got a lot of encouragement, especially from friends in the industry who had lost band members, telling us that we needed to continue,” he says. “At first, it was tough because we didn’t even know if it was possible to keep Gov’t Mule going, but we had a lot of friends like Dave Schools (Widespread Panic) and Les Claypool (Primus) and Mike Gordon (Phish) and George Porter, Jr. (The Meters), and Jason Newsted (Metallica) and a lot of other wonderful bass players who kept us on the road by volunteering their services, and we’ve kind of moved forward the best we know how since then.”

Before we move on with our story, let’s just pause for a second and enjoy the idea of Metallica’s Jason Newsted onstage with Gov’t Mule.

Now then, as we were saying …

Since then, Haynes has led Gov’t Mule through night after night (and album after album) of jam-heavy Southern rock with his gruff, soulful shout and bee-sting lead guitar, and for the last decade or so, the lineup has been stable, allowing the quartet to deepen their already first-rate level of musical communication.

“The best thing that can happen to any band, especially one that relies on improvisation and embraces a jazz philosophy, is to be able to stay together a long time,” he says. “As great as the chemistry may be in the beginning, it just gets better and better the more you learn each other’s personalities and musical vocabularies. It becomes somewhat telepathic. There’s a form of chemistry that can only happen by allowing that relationship to grow over many years. That’s why bands get better as they stay together.”

But there’s another factor in the Mule’s unpredictable sound that Haynes is more than happy to pay tribute to: The band’s audience, a fiercely dedicated lot that tends to hit multiple shows on each tour and trade recordings of their favorite performances.

“Our audience is a huge part of the picture,” Haynes says. “From the beginning, and more so year after year, our audience has expected us to go somewhere unexpected. We’re lucky that we have an audience that allows us to do that and wants to be part of the journey.”