Residents also reported hearing gunshots and the American children at a soft play area in the village were said to have "suddenly left" after the incident.
A police car was blocking the entrance to the base and there was a strong police presence in the area, with 4x4 vehicles patrolling outside.
A Suffolk Police spokesman said: "Suffolk Police were contacted at approximately 1.40pm today to reports of a disturbance at RAF Mildenhall in Suffolk.
"The base was put into lockdown and units responded immediately. Shots were fired by American service personnel and a man has been detained with cuts and bruises and taken into custody.
"No other people have been injured as a result of the incident. Suffolk Police remain on site."
The force also tweeted: "Members of the public are asked to avoid the area around RAF Mildenhall for the time being."
And it later said: "As there is considered no ongoing threat to the community relating to the incident at RAF Mildenhall, schools can continue to operate as they normally would at the end of a day."
No other police forces are thought to be involved in the incident at this stage. Suffolk Police were unable to confirm if the matter was being treated as terrorist-related.
But the force said that while the incident was ongoing, there was no wider threat to the public, or base occupants.
In November last year the then Defence Secretary Sir Michael Fallon said RAF Mildenhall was one of 56 Ministry of Defence sites earmarked for closure.
The base, which is due to shut in 2022, is home to the US Air Force's 100th Air Refuelling Wing and 352nd Special Operations Wing.
A member of staff at Jumppin Jacks Funhouse in Mildenhall said: "All the American children playing here suddenly left, but we didn't hear anything or know why."
A statement on the base's Facebook page said: "RAF Mildenhall locked down at 1pm today following reports of a disturbance on base.
"The base was locked down and emergency personnel are responding to the situation. Additional details will be provided as they become available."
A Pentagon spokesman in Washington said: "The security incident has been contained and a suspect has been apprehended."
RAF Mildenhall locked down at 1 p.m. today following reports of a disturbance on base. The base was locked down and...
Posted by RAF Mildenhall on Monday, 18 December 2017
And a US Air Force spokesman said: "The incident has been contained. There is a suspect that has been apprehended."
BBC home affairs correspondent Daniel Sandford tweeted: "The early indications are that someone tried to drive onto the base, and was stopped at the gate, and has been arrested. People nearby heard gunshots."
Shortly before 3pm (local time), two businesses on the base confirmed they were no longer on lockdown after the security alert.
The 470ha base, which houses about 3100 US military and an additional 3000 family members, is used by the US to refuel US and Nato aircraft in Europe.
RAF Mildenhall is set for closure after the US said it was going to move is operations from there to Germany. The site has previously been a potential terror attack target.
In May 2016, delivery driver Junead Khan, from Luton, who planned to attack US servicemen outside RAF Mildenhall, was jailed for life.
Islamic extremist Khan wanted to attack US airmen in East Anglia with a knife like that used by Jihadi John after plotting with an ISIS fighter in Syria.
He delivered medical supplies to Boots, Superdrug, Morrisons Supermarket and Co-Op along with hospitals and surgeries on behalf of Alliance Healthcare.
His routes took him to East Anglia and to two Lloyd's pharmacies in the village of Mildenhall, close to two US airbases.
RAF Mildenhall and neighbouring RAF Lakenheath were re-opened after World War II to host B-29 Superfortresses and have hosted US airmen ever since.
Also last year, an abduction scare forced police to launch a major manhunt after an airman was attacked at knifepoint while out jogging near RAF Marham in Norfolk.
The two suspects were at first suspected to be jihadis plotting a terror attack. But another theory now is that it may have been a failed mugging.