A method and system for aligning the duration of supplemental content with the duration of modifiable content in content modification operations. An example method includes determining a duration of a modifiable content segment in a media sequence being received by a content-presentation device. The example method then includes identifying a supplemental content segment to replace the modifiable content segment and selecting from a predefined set of multiple different-duration versions of the identified supplemental content segment, a particular instance of the identified supplemental content segment based on the particular instance of the identified supplemental content segment having a duration closest to the determined duration of the modifiable content segment. The method further includes causing the selected particular instance of the identified supplemental content segment to be transmitted to the content-presentation device to facilitate dynamic replacement of the supplemental content segment with the particular instance of the identified supplemental content segment.