Kanto Route 6

In Generations I and III, the layout of Route 6 is basically the same. The depiction of Route 6 is almost identical in Generations I and III, however there are still several minor changes in the made within the layout. The fields on the northern-most tips of the route have greatly increased in size, while the area of tall grass has also grown dramatically adding an extra layer. Apart from this, most aesthetic features have been enhanced. Trees have become bigger, the cement road has been changed to a gravel path, flowers are more visible and most other sprites have been upgraded to Generation III standards.

In Generation II, the route was drastically shortened. The pond was cut in half length-wise, while the area of tall grass was also cut shorter. The pond figure changed dramatically, and has curled around the outside on the southwestern part of the route, forming a backward "L" shape. The fields on the northern-most tips of the route have greatly decreased in size, while the area of tall grass has also shrunken dramatically, forming a little patch of tall grass around the place. Also, there are no Trainers on the route in Pokémon Gold and Silver; however, there are two in Crystal.

Route 6 has changed completely in its Generation IV appearance while the layout has changed dramatically. Route 6 can be accessed two ways from the northern side: from the gate coming from Saffron City, or the Underground Path which leads directly from Route 6. Coming from the Saffron City entrance, the route goes through a set of ledges down to a dirt road which forms a "T" intersection. The ledges east and west of the gate are no longer present, and are replaced by a small ledge on the northwestern corner of the route. After the player jumps down the southern set of ledges, they will find themselves on a dirt road of which it forms a "T" intersection, surrounding itself by tall grass. By going east at the intersection, Trainers can reach the Underground Path building of which the second northern terminus begins.

From the Underground Path building, the dirt road will turn west and follow parallel to the large patch of tall grass until it forms the "T" intersection, of which going west leads no where, while going south will lead Trainers along a winding, however, shortened track to Vermilion City. By traveling south, the road will turn through the large patch of tall grass coming from east and west of the pathway. The route then swivels east ahead of a large pond's water front, which will then return south again along the pond's eastern shoreline, which will then travel along a straight north-south path to Vermilion City. The large pond is now located in the center of the route, and Trainers are able to follow the west shoreline by traveling to the western corner which is covered by tall grass. Because the position of the Vermilion entry is moved, there now is a path to the western side of the track that does a loop around, while having a patch of tall grass in the center of the looped track. Like in Generation II, the route has decreased in size; a change like this is rare in the Generation IV remakes, as HeartGold and SoulSilver have typically kept routes similar in size to that of FireRed and LeafGreen.

Route 6 made a brief appearance in Kalling Kadabra, where Blue was not allowed into Saffron City via the gate.

In Storming the Forretress, Silver told his Ursaring to take his father to his eighteenth hideout, located on Route 6. When he later went to the hideout himself, neither Ursaring or his father could be found there.