The first known settlers of the area appeared sometime after the last ice age. Merrimack is a Native American term meaning sturgeon, a type of fish. The Pennacook people named the Merrimack River after this fish because of the vast population that once existed there. The Pennacooks spelled it Monnomoke or Merramake.

"When the town was incorporated, it took the name of the river and spelled it Merrymac," according to the Merrimack Historical Society.The first mention of the territory containing the current town of Merrimack among written records was the petition of Passaconaway to the General Court of Massachusetts for a grant of land to include a part of this region.

This was in 1662, and in the autumn of that year the court acceded to the request, and the aged sachem and his associates were granted a strip of country a mile and a half wide on both banks of the Merrimack at this section of the river. Although the boundaries of this grant are not specifically known today, it is probable that the chieftain held at least a portion of the current town of Merrimack.

European settlers first came to the area in the late 17th century when the area was still in dispute between the Province of New Hampshire and Massachusetts Bay Colony. The town of Merrimack was originally part of the 1673 Dunstable grant. On June 25, 1734, Massachusetts granted the town organization as "Naticook", which was made up of Litchfield and part of Merrimack.

In 1746 the boundary line between Massachusetts and New Hampshire was revised, and the land which was originally part of Massachusetts became part of New Hampshire. When it went back into New Hampshire, the province disincorporated the towns of Dunstable, Naticook, and Nottingham and formed it into one giant territory again, roughly the size of the old Dunstable Grant from the 1670s.On April 2, 1746, Governor Benning Wentworth signed a charter establishing that the land from Pennichuck Brook to the Souhegan River became the Town of Merrymac.

At that time fewer than 50 families lived here. Pawtucket, Nashaway and Pennacook people camped along the banks of the Merrimack and Souhegan rivers. The Pennacooks were greatest in numbers, and their chief, Passaconaway, was the ruler of all the tribes in the Merrimack Valley. On June 5, 1750, the town's charter was ratified, giving the town an additional 3 miles (5 km) to the north.

The new portion called "Souhegan East" was made up of the land north of the Souhegan River. Matthew Thornton, a signer of the Declaration of Independence, lived and was buried in Merrimack. The Signer's House and Matthew Thornton Cemetery are still located in the town. The original meetinghouse was built at the exact center of town.

There were two cemeteries. Turkey Hill on Meetinghouse Road is the first mentioned in the town records, but Thornton Cemetery on Route 3 has the oldest gravestone. The nineteenth century saw much growth in Merrimack. The meetinghouse was too small and too far from what had become the center of town.

The church and government became separate and two new churches were built in more convenient locations, one in South Merrimack and one on Baboosic Lake Road. A new town hall was built to replace the meetinghouse.The Boston and Maine Railroad laid tracks through the town in the 19th century, with several stations operating until the mid-20th century, when the advent of the automobile transformed Merrimack from a largely agricultural community to a bedroom community of Boston and nearby cities in New Hampshire.

Since 1970 the town has been the home of an Anheuser-Busch brewery, their easternmost, and one of their smallest plants in the United States. It is home to a brewery tour and one of the five stables for the Budweiser Clydesdales.The Merrimack School Board attracted national attention in 1995 when it passed a "prohibition of alternative lifestyle instruction" act, which resulted in the removal of a work by William Shakespeare from the school curriculum.

The board members who supported the act were voted out in the subsequent board election.