Before the real game begins, a third party randomly places the possible winnings in the cases, which are distributed to 26 models (identically dressed, which is taken from the original Dutch version but without wigs) who reveal the contents during the game. No one, including the host, knows what amount in the cases. Each contestant receives a new, randomly assigned set of cases. The winnings range in amounts from $0.01 to the top prize.

The show's mysterious banker makes an offer to buy the contestant's chosen case.After picking his/her case, the contestant then selects 6 of the remaining 25 cases, revealed one at a time. This is followed by a "phone call" by "The Banker", a mysterious figure whose face is not shown (at times a silhouette can be seen). He purportedly sits in a skybox (situated between the two audience sections) and makes an offer, via telephone to Mandel (his voice is never heard) to buy the contestant's case based on the cash amounts still in play and the player's psychology (supposedly insulting comments have been relayed to the contestant; in one episode a rabbit-owning contestant was informed that The Banker, after making his offer, "was going rabbit hunting"; in another with a boxer, he made a comment seeing if she could "take a punch". ). The player is then asked by Mandel the title question: "Deal or No Deal?".

If the contestant accepts the buyout (by stating "Deal!"), they must lift a cover and press a button to confirm the decision. The game then ends, and the contents of the case that s/he chose at the beginning of the game are then revealed along with the whereabouts of the top remaining prizes. Sometimes, Howie lifts the cover for the contestant, especially during more dramatic decisions. In recent episodes, however, he seems to be lifting the cover almost every time. The contestant does not necessarily have to say "Deal!"; only hitting the button is necessary.

Should the contestant refuse the offer (by stating "No deal!"), they must choose five of the remaining cases to eliminate from consideration. The Banker makes another offer, and play continues as before. The Banker's offer may be higher or lower than the previous offer (if a top prize is eliminated, generally the offer decreases; conversely, if lower amounts are eliminated the offer increases significantly). The contestant can simply close the cover to imply "No Deal" without actually saying the phrase.

Subsequent rounds have the contestant withdrawing four, three, then two cases from play; should the contestant continue to decline The Banker's offer after this point, they then eliminate one case each time (with an intervening offer from The Banker) until two cases are left. If the player rejects the final offer, they receive whatever cash amount is contained inside the case that they originally chose. Earlier shows gave the contestant a chance to switch their case with the one remaining in the gallery, but this offer has not been made in the more recent shows.

Each contestant has several supporters (usually, three or four), who sit in a special section just off stage during his/her game. As the field of briefcases dwindles, one or more of the supporters are asked to consult with the contestant and help him/her make a decision. These exchanges have become emotional, particularly when very high and very small amounts remained and The Banker offers a large cash buyout; on at least one occasion, the contestant's daughters called, pleading (successfully) with her to take The Banker's deal. The contestant's supporters are typically revealed on the second Bank deal.