The centre back arrives on a free transfer having turned down the offer of a new deal at Brisbane Road.
The 24-year-old, described as a quick, modern-day defender, has signed a two-year deal with the option to extend by a further 12 months.
“I’m so happy to be here and I can’t wait to get started," Ekpiteta said.
“I’ve spoken to Neil and the club is oozing positivity at the moment, so I feel this is a perfect opportunity to show what I can do.
“I love to defend and am also confident to play with the ball at my feet when the time is right, so I feel I have a lot to offer to Blackpool.”
Ekpiteta, who has been capped by Nigeria’s Under-20 side as well as England C, came through the youth ranks at Oxford United.
The 6ft 4ins defender had to drop down to non-league to get his chance, playing for the likes of Witham Town, Concord Rangers and East Thurrock United.
He got his move to Orient in January 2018, helping the O’s win the National League title under the late Justin Edinburgh in his first full season.
He went on to make 79 appearances in total, scoring six times.
His brother Marvel, also a defender, plays for Newport County in League Two.
The Seasiders were keen to add to their defensive ranks following the departures of loanees Ben Heneghan and Taylor Moore.
That left them with just Jordan Thorniley, Ryan Edwards, James Husband Michael Nottingham who are capable of playing in the centre of defence.
Head coach Neil Critchley said: “Marvin is an exciting young defender with bags of potential and we’re thrilled to have him here.
“He’s a player who has progressed from non-league and has impressed everywhere he has been and this is the next step in his career.
“He’s an athletic defender, who will be a wonderful asset to the squad going forward.”
Ekpiteta joins Swindon Town forward Keshi Anderson in making the move to Bloomfield Road the summer.
The club are also expecting to announce further news later today.