Runner-up a record five times, the American, who will turn 43 on Sunday, shares the lead at the halfway stage with countryman Billy Horschel, who missed the cut at the 2006 US Open, his only previous major.
But there are 30 players grouped within four shots off the lead and those include the top two players in the world, Tiger Woods and Rory McIlroy.
Mickelson expects 101-year-old Merion Golf Club in suburban Philadelphia to continue to play tough with the cold, damp conditions that marked most of the first two days giving way to hot, sunny weather over the weekend.
"I don't know how anyone is going to separate too far from the field," the four-time major winner said.
"There might be a hot round tomorrow and there might be a hot round on Sunday, but it's unlikely to be the same player."
A Mickelson win on Sunday would be a massive story given the popularity that surrounds the left-hander from California, his quintet of near misses and the fact that it would come both on his 43rd birthday and Father's Day.
But there were some intriguing sub-plots emerging from the chasing pack.
English hopes of a first US Open winner since Tony Jacklin 43 years ago and a first major champion since Nick Faldo 17 years ago were high with both Luke Donald and Justin Rose on level par, just one stroke off the lead.
Ian Poulter at two over makes it a triple English threat, from three of Europe's Ryder Cup heroes, and all three say that they now have the experience and confidence to go all the way.
Former world number one Donald, who will join Mickelson and Horschel in the last grouping, believes that Merion, with it's premium on tidy tee-shots, wondrous wedge play and pinpoint putting, is ideally suited to his game.
"Obviously I haven't played very well (at US Opens), but when I saw this place last week, I thought it was a good fit for my game," he said.
Hopes of another Australian win at Merion, 32 years after David Graham became the first player from that country to win the US Open, will rest with John Senden, who is at one over, and Mathew Goggin, a stroke further back.
Steve Striker, matching Donald and Rose at level par, at 46 would become the oldest winner of the US Open, while Ernie Els, on three over, seeks to add the US Open crown to the Brirtish Open he won last year.
Then there are Woods and McIlroy, who will play together for the third straight day after identical rounds of 73-70.
A total of 73 players made the cut when the second round finished behind time on Saturday morning and third-round play in the afternoon will consist of threesomes going off from holes 1 and 11.