Route 133 begins at the junction of Route 38 and Route 110 in Lowell, where Route 110 begins a concurrency with Route 38 northbound.
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Route 133 passes the northern end of Route 22 near the crossing of the Essex River before Route 133 heads into Gloucester.
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In Andover, Route 133 crosses I-93 at Exit 43 and continues eastward, bypassing the town center to the north as it crosses Route 28.
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The two routes cross the historic Choate Bridge over the Ipswich River concurrently, before turning southward, passing through the historic village before splitting once more, with Route 133 heading east-southeastward into Essex.
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In Georgetown, Route 133 passes south of the Lufkins Brook Area before meeting Route 97 for a short concurrency that lasts for a tenth of a mile.
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