At the north end of the interchange, the highway briefly re-enters the town of Perryville, intersects the ramps to and from southbound I-95 and the entrance to Hollywood Casino Perryville, and passes west of a park and ride lot before it reaches a four-way intersection with the northern end of MD 824 (Blythedale Road) and the southern end of MD 275 (Perrylawn Drive). At this intersection, MD 222 turns west onto Bainbridge Road toward Port Deposit. MD 222 heads west through farmland, crossing Happy Valley Branch before passing the entrance to the former United States Naval Training Center, Bainbridge, which contains the Edward W. Haviland House and the original campus of the Tome School. The highway descends from a high bluff to the Susquehanna River, during which southbound MD 222 has a climbing lane. Upon entering the town limits of Port Deposit, MD 222's name changes to Main Street and the highway makes a sharp turn to the north to parallel the river and Norfolk Southern Railway's Port Road Branch. The state highway intersects MD 276 (Center Street) in the center of Port Deposit. MD 222 passes the Paw Paw Building and intersects Granite Avenue before crossing Rock Run and passing under a low railroad bridge to the west side of the tracks. The highway leaves the town of Port Deposit and continues north as Susquehanna River Road, closely paralleling the river and passing through a unit of Susquehanna State Park along the river. Soon after crossing Octoraro Creek, MD 222 reaches its northern terminus at an intersection with US 1 (Conowingo Road) at the eastern end of Conowingo Dam. Following US 1 northeast to the community of Conowingo leads to the southern terminus of US 222. MD 222 is a part of the National Highway System as a principal arterial from US 40 north to MD 275 within Perryville. What is now MD 222 was originally designated MD 268. MD 268 was replaced by a southern extension of US 222 from US 1 at Conowingo to US 40 (now MD 7) in Perryville in 1938. The Susquehanna River Road section of US 222 was transferred from state to county maintenance through a May 8, 1958, road transfer agreement. However, that section was returned to state control through an August 23, 1961, agreement after Cecil County requested it be returned to the state. The American Association of State Highway and Transportation Officials (AASHTO) approved rolling back the southern end of the US 222 designation from US 40 to US 1 at their April 1995 spring meeting.